Studies are being made A) on isolating and defining previously unknown modulators of fibrinogen synthesis and on the effects on fibrinogen synthesis of known "inflammatory" hormones; and B) on the regulation of the intravascular activity of thrombin by circulating antiproteases. Supplementary funds are requested to support the latter studies in dogs. In particular, funds are requested for developing a rapid method of preparing dog antithrombin III (AT3) in its native state, of labelling it with radioactive iodine, I, without any alteration of its activity, and of studying the normal metabolism of I-AT3 in the dog circulation and the reactions of I-AT3 in vivo with circulating thrombin. Bovine or dog thrombin will be injected into the circulation or liberated from precursors. We have developed a simple preparation of AT3 which we think will meet our requirements. The above studies should not only throw much light on mechanisms localizing the action of thrombin released in the animal circulation but are preliminary to studies later proposed on the metabolism and actions of antithrombin III in man.